Glycoprotein Non-Metastatic Protein B (GPNMB): The Missing Link Between Lysosomes and Obesity

Abstract

As a result of an unhealthy diet and limited physical activity, obesity has become a widespread pandemic worldwide and is an important predictor for the development of cardiovascular disease. Obesity is often characterized by a pro-inflammatory environment in white adipose tissue (WAT), mainly due to increased macrophage infiltration. These immune cells boost their lipid concentrations by accumulating the content of dying adipocytes. As the lysosome is highly involved in lipid handling, the progressive lipid accumulation may result in lysosomal stress and a metabolic shift. Recent studies have identified glycoprotein non-metastatic melanoma protein B (GPNMB) as a novel marker of inflammatory diseases. GPNMB is a type I transmembrane protein on the cell surface of various cell types, such as macrophages, dendritic cells, osteoblasts, and microglia, from which it can be proteolytically cleaved into a soluble molecule. It is induced by lysosomal stress via microphthalmia-associated transcription factor and thus has been found to be upregulated in many lysosomal storage disorders. In addition, a clear connection between GPNMB and obesity was recently established. GPNMB was shown to have protective and anti-inflammatory effects in most cases, preventing the progression of obesity-related metabolic disorders. In contrast, soluble GPNMB likely has the opposite effect and promotes lipogenesis in WAT. This review aims to summarize and clarify the role of GPNMB in the progression of obesity and to highlight its potential use as a biomarker for lipid-associated disorders.

Ethnic Variations in the Levels of Bone Biomarkers (Osteoprostegerin, Receptor Activator of Nuclear Factor Kappa-Β Ligand and Glycoprotein Non-Metastatic Melanoma Protein B) in People with Type 2 Diabetes

“…Our previous data along with other recent studies have demonstrated increased circulating levels of GPNMB in those with metabolic diseases [13,30,31]. A distinct correlation has been established between GPNMB and obesity, wherein GPNMB plays a protective role, with anti-inflammatory effects preventing the progression of obesity-related metabolic complications [32]. GPNMB can be proteolytically cleaved into a soluble molecule by lysosomal stress [33].…”

“…The soluble GPNMB is suggested to have an opposite effect, stimulating lipogenesis in white adipose tissue (WAT), resulting in a positive correlation between soluble GPNMB and obesity. This explains the important role of this protein in metabolic disorders [32]. Interestingly, some studies showed that transgenic mice that overexpressed GPNMB showed increased bone resorption [34].…”